Local and global calcium signals and fluid and electrolyte secretion in mouse submandibular acinar cells

Polarized Ca2+ signals that originate at and spread from the apical pole have been shown to occur in acinar cells from lacrimal, parotid, and pancreatic glands. However, "local" Ca2+ signals, that are restricted to the apical pole of the cell, have been previously demonstrated only in pancreatic acinar cells in which the primary function of the Ca2+ signal is to regulate exocytosis. We show that submandibular acinar cells, in which the primary function of the Ca2+ signal is to drive fluid and electrolyte secretion, are capable of both Ca2+ waves and local Ca2+ signals. The generally accepted model for fluid and electrolyte secretion requires simultaneous Ca2+-activation of basally located K+ channels and apically located Cl- channels. Whereas a propagated cell-wide Ca2+ signal is clearly consistent with this model, a local Ca2+ signal is not, because there is no increase in intracellular Ca2+ concentration at the basal pole of the cell. Our data provide the first direct demonstration, in submandibular acinar cells, of the apical and basal location of the Cl- and K+ channels, respectively, and confirm that local Ca2+ signals do not Ca2+-activate K+ channels. We reevaluate the model for fluid and electrolyte secretion and demonstrate that Ca2+-activation of the Cl- channels is sufficient to voltage-activate the K+ channels and thus demonstrate that local Ca2+ signals are sufficient to support fluid secretion.